Joshua F. Knox

Inhibitory Control Test for the Diagnosis of Minimal Hepatic Encephalopathy

BACKGROUND & AIMS Minimal hepatic encephalopathy (MHE) is difficult to diagnose. The Inhibitory Control Test (ICT) measures response inhibition and has diagnosed MHE with 90% sensitivity and specificity in a selected population; high lure and low target rates indicated poor ICT performance. We studied the reliability and validity of ICT for MHE diagnosis. METHODS ICT was compared with a psychometric battery (standard psychometric tests [SPT]) for MHE diagnosis and overt hepatic encephalopathy (OHE) prediction. ICT was administered twice for test-retest reliability, before/after transvenous intrahepatic portosystemic shunting (TIPS), and before/after yogurt treatment. The time taken by 2 medical assistants (MA) to administer ICT was recorded and compared with that of a psychologist for cost analysis. RESULTS One hundred thirty-six cirrhotic patients and 116 age/education-matched controls were studied. ICT (>5 lures) had 88% sensitivity for MHE diagnosis with 0.902 area under the curve for receiver operating characteristic. MHE-positive patients had significantly higher ICT lures (11 vs 4, respectively, P = .0001) and lower targets (92% vs 97%, respectively, P = .0001) compared with MHE-negative patients. The test/retest reliability for ICT lures (n = 50, r = 0.90, P = .0001) was high. ICT and SPT were equivalent in predicting OHE (21%). ICT lures significantly worsened after TIPS (n = 10; 5 vs 9, respectively; P = .02) and improved after yogurt supplementation (n = 18, 10 vs 5, respectively; P = .002). The MAs were successfully trained to administer ICT; the time required for test administration and the associated costs were smaller for ICT than for SPT. CONCLUSIONS ICT is a sensitive, reliable, and valid test for MHE diagnosis that can be administered inexpensively by MAs.

Unsedated transnasal endoscopy: a new technique for accurately detecting and grading esophageal varices in cirrhotic patients

OBJECTIVES:Endoscopic screening of cirrhotics for large esophageal varices (EV) is advocated before initiation of prophylactic therapy for variceal bleeding. Conscious sedation for conventional endoscopy is problematic in cirrhotic patients because of risk of prolonged encephalopathy. Unsedated transnasal endoscopy (T-EGD) is a new technique, which allows for unsedated examination because it is well tolerated. The aims of this study were to determine whether T-EGD is feasible for screening of cirrhotic patients for presence of EV and to compare the diagnostic yield of T-EGD with conventional endoscopy for detecting and grading of EV.METHODS:Fifteen cirrhotics with no history of variceal bleeding, known EV, severe thrombocytopenia, or recurrent epistaxis were evaluated by unsedated T-EGD using a 5.3-mm outer diameter endoscope. Immediately afterward, a different endoscopist, blinded to T-EGD findings, performed sedated conventional endoscopy in standard fashion. The presence and size of EV, gastric varices, and other findings were recorded. Patient tolerance was also evaluated.RESULTS:Both modalities detected EV in the same 10 and gastric varices in the same two patients and completely agreed on size of EV. No stigmata of recent variceal bleeding were noted. Average time for unsedated T-EGD was 5 min 6 s. All patients found both procedures acceptable overall, with no significant difference in choking, discomfort, and sore throat. One patient developed self-limited epistaxis after T-EGD.CONCLUSIONS:1) EV are accurately detected and graded by T-EGD in cirrhotic patients. 2) T-EGD is a safe and less costly screening alternative for EV in cirrhotic patients.

Leflunomide treatment of Crohn's disease patients intolerant to standard immunomodulator therapy.

Background Immunomodulator therapy with the purine analogs azathioprine and 6-mercaptopurine (6-MP), is efficacious in the treatment of moderate to severe Crohns disease (CD), but is not tolerated by a significant minority of patients. The pyrimidine analog, leflunomide, has demonstrated efficacy in the treatment of rheumatoid arthritis (RA) patients. Because established RA immunomodulator agents may demonstrate success in the treatment of CD, we reviewed our clinical open-label experience with leflunomide in a refractory CD population. Goals Assess the effect of leflunomide 20 mg daily, on disease activity, steroid requirement and serologic measures of inflammatory activity in our series of CD patients intolerant to azathioprine/6-MP. Study CD patients intolerant of azathioprine/6-MP were offered leflunomide treatment. The Harvey-Bradshaw (H-B) disease activity index, global assessment, serologic parameters and ability to taper corticosteroids of those who accepted were retrospectively assessed. Results Leflunomide was well tolerated and resulted in a significant reduction in the H-B score, global assessment and serologic parameters in 8/12 patients. Average follow-up was 38 weeks and a majority of steroid-dependent patients were able to successfully taper following leflunomide initiation. Conclusions Our case series demonstrates that the pyrimidine analog leflunomide may be effective for treating moderate to severe CD patients intolerant to standard immunomodulator therapy and warrants further investigation in a randomized controlled trial.

The irony of herbal hepatitis: Ma-Huang-induced hepatotoxicity associated with compound heterozygosity for hereditary hemochromatosis.

We report the case of a 44-year-old Caucasian man who was referred to our hepatology clinic because of jaundice of unclear etiology with elevated aminotransferases. The patient had been healthy and well with normal liver chemistries noted at an insurance examination six months prior to presentation. Approximately five months prior to presentation, he began using a dietary supplement, Hydroxycut, intended for weight loss, which he discontinued because of satisfactory weight loss six weeks before presentation. Four weeks later, his wife had started noticing yellowish discoloration of his eyes and skin. The patient also noted ashen stools and dark urine for approximately the same duration. He denied nausea, abdominal pain and swelling, pruritus, alteration of sleep–wake cycle, or change in mental status or in handwriting. He had a recent 30–lb intentional weight loss. He denied shortness of breath, chest pain, tremulousness, palpitations, and headaches. The patient’s aminotransferases at his primary physician’s office were: ALT 3600 IU/liter and AST 2046 IU/liter, and his total bilirubin was 3.5 mg/dl. The primary physician also obtained an abdominal ultrasound and CT scan, hepatitis A lgM and hepatitis B and C serologies, all of which were negative. Repeat liver enzymes were ALT 1046 IU/liter and AST 372 IU/liter with a total bilirubin 2.5 mg/dl, ferritin of 6882, iron 266, and transferrin 225. He was then referred to us for evaluation. Past medical history included hepatitis A ten years prior with spontaneous resolution and asthma under excellent control with inhaled medications. The family history was noncontributory.

High-dose vitamin E supplementation does not diminish ribavirin-associated haemolysis in hepatitis C treatment with combination standard alpha-interferon and ribavirin

Background : Ribavirin is associated with haemolytic anaemia. Antioxidants have been reported to decrease severity of this anaemia.